Research Progress and Clinical Translational Application of Ultrasound Localization Microscopy in Microcirculation Imaging

Abstract As an emerging super-resolution ultrasound imaging technology, ultrasound localization microscopy (ULM) breaks the acoustic diffraction limit of conventional ultrasound. By localizing and tracking individual microbubble contrast agents at the sub-wavelength scale, ULM achieves high-precision visualization and quantitative evaluation of micron-level microvascular structures and hemodynamic parameters. Compared with traditional color Doppler flow imaging and contrast-enhanced ultrasound, ULM possesses superior spatial resolution and microcirculation quantification capability, enabling in-depth analysis of microvascular morphological remodeling and functional perfusion abnormalities. This review summarizes the core technical principles, optimized algorithms, and key technical bottlenecks of ULM, including microbubble signal separation, single-bubble localization accuracy, physiological motion artifacts, and prolonged acquisition duration. Furthermore, we comprehensively elaborate the preclinical and clinical application progress of ULM in multiple systems, covering neurovascular, renal, tumor, cardiovascular, endocrine and cardiac microcirculation diseases, with a specific focus on its novel clinical value in identifying vulnerable carotid atherosclerotic plaques. We also discuss the current limitations restricting large-scale clinical translation, standardized protocol establishment, and deep-tissue imaging performance of ULM, noting that the majority of existing human ULM evidence is still at the feasibility stage and large-scale prospective multi-center clinical validations are still needed. Targeting the above-mentioned translational bottlenecks, finally, this review prospects the future development directions of ULM, including artificial intelligence optimization, three-dimensional whole-organ imaging, multi-modal and multi-omics fusion. With continuous technical iteration, ULM is expected to become a novel non-invasive imaging modality for early diagnosis, risk stratification and therapeutic efficacy evaluation of microcirculation-related disorders.